Value of p16/Ki67 Dual Immunostaining Evaluation of Cervical Cytology Specimen
Leonardo Rodriguez-Carunchio, Victoria Fuste, Tatiana Benavides, Paola Castillo, Agata Rodriguez, Immaculada Alonso, Aureli Torne, Marta del Pino, Jaume Ordi. Hospital Clínic - CRESIB (Centre de Recerca en Salut Internacional de Barcelona), Barcelona, Spain; Hospital Clínic - Institut d´Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
Background: Early diagnosis of cervical cancer is based on the detection of high-grade cervical intraepithelial neoplasia (CIN2-3). Although conventional cytology has a high diagnostic specificity has a poor sensitivity. On the other hand, molecular techniques of detection of hr-HPV markedly improve sensitivity but significantly reduce the specificity. It has recently been proposed that the use of p16/Ki67 dual immunostaining in cytological specimens could improve the accuracy of these tecniques. The main objective of this study is to assess the sensitivity and specificity of p16/Ki67 dual staining and compare it with the results of VPH detection using Hybrid Capture 2 (HC2).
Design: From October 2009 to July 2011, 527 women were included in the study (mean age: 35.8±10.9 years). All of them were referred to the colposcopy unit of the Hospital Clinic of Barcelona due to abnormal cytology results. Digital colposcopy, liquid-based cytology specimen (ThinPrep®), hr-HPV detection using HC2 (Qiagen) were obtained in all cases, and colposcopically directed biopsy and/or endocervcial curettage when clinically indicated. p16/ki67 dual immunostaining in cytology (CINtec plus, mtm) were performed in all cases. Definitive diagnosis was established after a complete study of the patients.
Results: After the completion of the study, 227 patients (43.1%) were classified as CIN2+, 153 (29.0%) as CIN1 y 147 (27.9%) as negative. A positive result for the dual immunostaining were detected in 91.6% of CIN2+, 51.6% of CIN1 and 6.8% of of the women with a negative study. A HC2 positive test was observed in 96.5% of CIN2+, 90.8% of CIN1 and 49.8% of the women with a negative study. The sensitivity, specificity, positive and negative predictive values for the identification of CIN2-3 of dual staining and HC2 are shown in table 1.
|Sensitivity||Specificity||Positive predictive value||Negative predictive value|
|P16/Ki67 dual staining||91.6%||70.3%||70.0%||91.7%|